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Kullmann, S. ; Singh, A.* ; Sehgal, R.* ; Eichelmann, F.* ; Sandforth, L. ; Wilms, B.* ; Jähnert, M.* ; Peter, A. ; Meyhöfer, S.* ; Walther, D.* ; Preissl, H. ; Häring, H.-U. ; Schulze, M.B.* ; Heni, M.* ; Birkenfeld, A.L. ; Schürmann, A.* ; Ouni, M.*

Circulating epigenetic signatures classifying brain insulin resistance in humans.

Sci. Transl. Med. 17:eadv7834 (2025)
Verlagsversion Postprint DOI PMC
Open Access Green
Brain insulin action plays an important role in metabolic and cognitive health, but there is no biomarker available to assess brain insulin resistance in humans. Here, we developed a machine learning framework based on blood DNA methylation profiles of participants who did not have type 2 diabetes with and without brain insulin resistance and detailed metabolic phenotyping. We identified 540 DNA methylation sites (CpGs) as classifiers of brain insulin resistance in a discovery cohort (n = 167), results that were validated in two replication cohorts (n = 33 and 24) with high accuracy (83 to 94%). All 540 CpGs were differentially methylated and annotated to 445 genes mapping to neuronal development and axonogenesis processes. Methylation patterns of 98 of 540 CpGs exhibited a strong and significant (P < 0.05) blood-brain correlation, indicating that blood cells are a reliable proxy to capture brain-specific DNA methylation changes. These blood-based epigenetic signatures could potentially serve in the future for the early detection of individuals with brain insulin resistance in a broad clinical setting.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Glucose-uptake; Sad Kinases; Sensitivity; Hyperinsulinemia; Hypothalamus; Overweight; Blood
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 1946-6234
e-ISSN 1946-6242
Zeitschrift Science Translational Medicine
Quellenangaben Band: 17, Heft: 810, Seiten: , Artikelnummer: eadv7834 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-001
Förderungen German research Association as a clinician scientist
German research Foundation
German diabetes Society (ddG)
German center for diabetes research
Brandenburg State
German Ministry of Education and Research (BMBF)
DOI 10.1126/scitranslmed.adv7834
WOS ID 001545554600006
Scopus ID 105013076457
PubMed ID 40768600
Erfassungsdatum 2025-11-05
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